An intron mutation in the human alpha 1(I) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II.
This study describes a homozygous, G----A transition at the moderately conserved +5 position within the splice donor site of intron 14 in the human alpha 1(I) collagen gene. The mutation reduced the efficiency of normal splice-site selection since the exon upstream of the mutation was spliced alternatively. Moreover, the extent of alternative splicing was sensitive to the temperature at which the mutant cells were grown, suggesting that the mutation directly affected spliceosome assembly. To achieve exon skipping, this effect must be propagated so as to disrupt the selection of a second splice site in the adjacent intron.
Bonadio
J
J
Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109-0650.
Ramirez
F
F
Barr
M
M
D000225:Adenine; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D003488:Cyanogen Bromide; D005796:Genes; D006147:Guanine; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010449:Peptide Mapping; D016133:Polymerase Chain Reaction; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing; D012016:Reference Values; D015183:Restriction Mapping
D015345:Oligonucleotide Probes; D012322:RNA Precursors; D006147:Guanine; D003094:Collagen; D000225:Adenine; D003488:Cyanogen Bromide